Our understanding of the relationship between the molecular structure of macromolecules and their biological function is constantly increasing. Advances in molecular biology have made the processes of isolating and characterizing macromolecules more routine. These advances have been accompanied by advances in techniques to solve, analyze, and predict the three-dimensional structures of macromolecules using X-ray crystallography, NMR spectroscopy, cryoelectron microscopy, and computational means (Drenth, J., Principles of Protein X-ray Crystallography 1999, Wiley, New York; Siegal et al., Curr Opin Chem Biol. 3(5):530-6, 1999; Kuhlbrandt and Williams, Curr Opin Chem Biol. 3(5):537-43, 1999; Burley et al., Nat Genet. 23(2):151-7, 1999; Uson and Sheldrick, Curr Opin Struct Biol. 2(5):643-8, 1999; Skolnick and Fetrow, Trends Biotechnol. 18(1):34-9, 2000; Gohlke and Klebe, Angew Chem Int Ed. 41:2644-2676, 2002). Also, the massive amounts of information produced by genome-sequencing projects is adding to the pool of molecules available for structural comparison.
This abundance of data can be applied to the design of ligands, provided that efficient methods of manipulating the data are developed and refined.